1. Technical Field of the Invention
The present invention relates to novel topically applicable dermocosmetic compositions comprising certain melatonin derivative depigmenting agents, for treating the skin of the face and/or the body, for the purpose of whitening the skin or for treating pigmentation blemishes.
2. Description of the Prior Art
At different periods in their lifetimes, certain individuals develop dark and/or colored blemishes on the skin and, more especially, on the hands, imparting to the skin a heterogeneous appearance. These blemishes are due to a considerable concentration of melanin in the keratinocytes located at the skin surface. The reason for this is that the melanocytes located deep in the epidermis produce melanin and deliver such melanin to the surrounding kertinocytes, which then rise to the surface of the epidermis, loaded with melanin.
The mechanism of formation of skin pigmentation, namely, the formation of melanin, is particularly complex and schematically includes the following principal mechanisms:
Tyrosine.fwdarw.Dopa.fwdarw.Dopaquinone.fwdarw.Dopachrome.fwdarw.Melanin
Tyrosinase is the essential enzyme involved in this reaction sequence. In particular, it catalyzes the reaction for the conversion of tyrosine into dopa (dihydroxyphenylalanine) and the reaction for the conversion of dopa into dopaquinone. This tyrosinase acts only when it is in a mature state, under the influence of certain biological factors.
An active species is recognized as being depigmenting if it acts directly on the vitality of the epidermal melanocytes in which melanogenesis takes place and/or if it interferes with one of the steps in the biosynthesis of melanin, either by inhibiting one of the enzymes involved in melanogenesis or by inserting itself as a structural analog of one of the chemical compounds of the synthetic chain of melanin, which chain may thus become blocked and ensure depigmentation.
The active species most commonly used as depigmenting agents are, more particularly, hydroquinone and derivatives thereof, in particular its ethers such as hydroquinone monomethyl ether and monoethyl ether. Although they exhibit a certain level of efficacy, these compounds are, unfortunately, not free of side effects taking account of their toxicity, which renders them complicated, or even dangerous, to use. This toxicity arises from the fact that they intervene in fundamental mechanisms of melanogenesis by killing cells which then present the risk of disturbing their biological environment and which consequently oblige the skin to eliminate them by producing toxins.
Thus, hydroquinone, the use of which is moreover legally limited to a concentration of 2%, is a compound which is particularly irritant and cytotoxic to melanocytes, and the total or partial replacement of which thus constitutes a desideratum in this art.
The application of harmless topical depigmenting substances which are of good efficacy is most particularly desired in order to treat regional hyperpigmentations caused by melanocyte hyperactivity, such as idiopathic melasmas which occur over the course of pregnancy ("pregnancy mask" or chloasma), or of estroprogestative contraception, localized hyperpigmentations caused by benign melanocyte proliferation and hyperactivity, such as senile pigmentation blemishes deemed actinic lentigo, accidental hyperpigmentations such as post-lesional cicatrization and photosensitization, as well as certain leucodermias such as vitiligo. For the latter hyperpigmentations, failing being able to repigment the damage to the skin, it is possible to depigment the areas of residual normal skin in order to provide the skin, as a whole, with a homogeneous white complexion.
2,5-Dihydroxyphenylcarboxylic acid derivatives or benzofuran derivatives are described for such purpose in EP-0,524,108 and EP-0,526,302.